Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC 27560, USA.
Nutrients. 2021 Jan 18;13(1):262. doi: 10.3390/nu13010262.
Due to the critical shortage of kidneys for transplantation, the identification of modifiable factors related to graft failure is highly desirable. The role of trimethylamine--oxide (TMAO) in graft failure remains undetermined. Here, we investigated the clinical utility of TMAO and its dietary determinants for graft failure prediction in renal transplant recipients (RTRs).
We included 448 RTRs who participated in the TransplantLines Cohort Study. Cox proportional-hazards regression analyses were performed to study the association of plasma TMAO with graft failure. Net Benefit, which is a decision analysis method, was performed to evaluate the clinical utility of TMAO and dietary information in the prediction of graft failure.
Among RTRs (age 52.7 ± 13.1 years; 53% males), the baseline median TMAO was 5.6 (3.0-10.2) µmol/L. In multivariable regression analysis, the most important dietary determinants of TMAO were egg intake (Std. β = 0.09 [95%CI, 0.01; 0.18]; = 0.03), fiber intake (Std. β = -0.14 [95%CI, -0.22, -0.05]; = 0.002), and fish and seafood intake (Std. β = 0.12 [95%CI, 0.03,0.21]; = 0.01). After a median follow-up of 5.3 (4.5-6.0) years, graft failure was observed in 58 subjects. TMAO was associated with an increased risk of graft failure, independent of age, sex, the body mass index (BMI), blood pressure, lipids, albuminuria, and the Estimated Glomerular Filtration Rate (eGFR) (Hazard Ratio per 1-SD increase of TMAO, 1.62 (95% confidence interval (CI): 1.22; 2.14, < 0.001)). A TMAO and dietary enhanced prediction model offered approximately double the Net Benefit compared to a previously reported, validated prediction model for future graft failure, allowing the detection of 21 RTRs per 100 RTRs tested, with no false positives versus 10 RTRs, respectively.
A predictive model for graft failure, enriched with TMAO and its dietary determinants, yielded a higher Net Benefit compared with an already validated model. This study suggests that TMAO and its dietary determinants are associated with an increased risk of graft failure and that it is clinically meaningful.
由于肾脏供体严重短缺，因此迫切需要确定与移植物失败相关的可改变因素。三甲胺氧化物（TMAO）在移植物失败中的作用仍不确定。在这里，我们研究了 TMAO 及其饮食决定因素在肾移植受者（RTR）中的预测移植物失败的临床实用性。
我们纳入了 448 名参加 TransplantLines 队列研究的 RTR。采用 Cox 比例风险回归分析研究血浆 TMAO 与移植物失败的关系。净效益是一种决策分析方法，用于评估 TMAO 和饮食信息在预测移植物失败中的临床实用性。
在 RTR 中（年龄 52.7 ± 13.1 岁；53%为男性），基线中位数 TMAO 为 5.6（3.0-10.2）µmol/L。多变量回归分析显示，TMAO 的最重要饮食决定因素是鸡蛋摄入（Std.β=0.09[95%CI，0.01；0.18]；=0.03），纤维摄入（Std.β=-0.14[95%CI，-0.22，-0.05]；=0.002）和鱼类和海鲜摄入（Std.β=0.12[95%CI，0.03，0.21]；=0.01）。中位随访 5.3（4.5-6.0）年后，58 例观察到移植物失败。TMAO 与移植物失败风险增加相关，独立于年龄、性别、体重指数（BMI）、血压、血脂、蛋白尿和估计肾小球滤过率（eGFR）（TMAO 每增加 1-SD 的危害比，1.62[95%置信区间（CI）：1.22；2.14，<0.001]）。与之前报道的验证后的预测模型相比，包含 TMAO 及其饮食决定因素的预测模型具有更高的净效益，能够检测到每 100 名 RTR 中约 21 名 RTR 出现移植物失败，且没有假阳性，而之前的模型仅能检测到 10 名 RTR 出现移植物失败。
一个包含 TMAO 及其饮食决定因素的移植物失败预测模型的净效益优于已经验证的模型。本研究表明，TMAO 及其饮食决定因素与移植物失败风险增加相关，且具有临床意义。
